Mechanisms underlying the impairment of hippocampal long-term potentiation and memory in experimental Parkinson's disease
Although patients with Parkinson's disease show impairments in cognitive performance even at the early stage of the disease, the synaptic mechanisms underlying cognitive impairment in this pathology are unknown. Hippocampal long-term potentiation represents the major experimental model for the...
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| Veröffentlicht in: | Brain (London, England : 1878) England : 1878), 2012-06, Vol.135 (Pt 6), p.1884-1899 |
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| creator | COSTA, Cinzia SGOBIO, Carmelo MORARI, Michele GRAZIA SPILLANTINI, Maria CLAUDIO LATAGLIATA, Emanuele PASCUCCI, Tiziana PUGLISI-ALLEGRA, Stefano GARDONI, Fabrizio DI LUCA, Monica PICCONI, Barbara CALABRESI, Paolo SILIQUINI, Sabrina TOZZI, Alessandro TANTUCCI, Michela GHIGLIERI, Veronica DI FILIPPO, Massimiliano PENDOLINO, Valentina DE LURE, Antonio MARTI, Matteo |
| description | Although patients with Parkinson's disease show impairments in cognitive performance even at the early stage of the disease, the synaptic mechanisms underlying cognitive impairment in this pathology are unknown. Hippocampal long-term potentiation represents the major experimental model for the synaptic changes underlying learning and memory and is controlled by endogenous dopamine. We found that hippocampal long-term potentiation is altered in both a neurotoxic and transgenic model of Parkinson's disease and this plastic alteration is associated with an impaired dopaminergic transmission and a decrease of NR2A/NR2B subunit ratio in synaptic N-methyl-d-aspartic acid receptors. Deficits in hippocampal-dependent learning were also found in hemiparkinsonian and mutant animals. Interestingly, the dopamine precursor l-DOPA was able to restore hippocampal synaptic potentiation via D1/D5 receptors and to ameliorate the cognitive deficit in parkinsonian animals suggesting that dopamine-dependent impairment of hippocampal long-term potentiation may contribute to cognitive deficits in patients with Parkinson's disease. |
| doi_str_mv | 10.1093/brain/aws101 |
| format | Article |
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Hippocampal long-term potentiation represents the major experimental model for the synaptic changes underlying learning and memory and is controlled by endogenous dopamine. We found that hippocampal long-term potentiation is altered in both a neurotoxic and transgenic model of Parkinson's disease and this plastic alteration is associated with an impaired dopaminergic transmission and a decrease of NR2A/NR2B subunit ratio in synaptic N-methyl-d-aspartic acid receptors. Deficits in hippocampal-dependent learning were also found in hemiparkinsonian and mutant animals. Interestingly, the dopamine precursor l-DOPA was able to restore hippocampal synaptic potentiation via D1/D5 receptors and to ameliorate the cognitive deficit in parkinsonian animals suggesting that dopamine-dependent impairment of hippocampal long-term potentiation may contribute to cognitive deficits in patients with Parkinson's disease.</description><identifier>ISSN: 0006-8950</identifier><identifier>EISSN: 1460-2156</identifier><identifier>DOI: 10.1093/brain/aws101</identifier><identifier>PMID: 22561640</identifier><language>eng</language><publisher>Oxford: Oxford University Press</publisher><subject>alpha-Synuclein - genetics ; Analysis of Variance ; Animals ; Antiparkinson Agents - pharmacology ; Antiparkinson Agents - therapeutic use ; Benserazide - pharmacology ; Benserazide - therapeutic use ; Biological and medical sciences ; Biophysical Phenomena - drug effects ; Biophysical Phenomena - genetics ; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases ; Disease Models, Animal ; Dopamine - metabolism ; Electric Stimulation ; Excitatory Postsynaptic Potentials - drug effects ; Excitatory Postsynaptic Potentials - genetics ; Excitatory Postsynaptic Potentials - physiology ; Exploratory Behavior - drug effects ; Hippocampus - physiopathology ; Humans ; Levodopa - pharmacology ; Levodopa - therapeutic use ; Long-Term Potentiation - drug effects ; Long-Term Potentiation - genetics ; Long-Term Potentiation - physiology ; Male ; Medical sciences ; Memory Disorders - drug therapy ; Memory Disorders - etiology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Microdialysis - methods ; Mutation - genetics ; Neurology ; Oxidopamine - toxicity ; Parkinson Disease - complications ; Parkinson Disease - drug therapy ; Parkinson Disease - etiology ; Parkinson Disease - pathology ; Patch-Clamp Techniques ; Radionuclide Imaging ; Rats ; Subcellular Fractions - drug effects ; Subcellular Fractions - metabolism ; Sympatholytics - toxicity ; Synaptosomes - diagnostic imaging ; Synaptosomes - drug effects ; Tritium - metabolism ; Tyrosine 3-Monooxygenase - metabolism</subject><ispartof>Brain (London, England : 1878), 2012-06, Vol.135 (Pt 6), p.1884-1899</ispartof><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c458t-7aee3fffdc150507d7d7dd508d242aa475aebde0aa4cdbff5e637eb36b52303b3</citedby><cites>FETCH-LOGICAL-c458t-7aee3fffdc150507d7d7dd508d242aa475aebde0aa4cdbff5e637eb36b52303b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25912265$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22561640$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>COSTA, Cinzia</creatorcontrib><creatorcontrib>SGOBIO, Carmelo</creatorcontrib><creatorcontrib>MORARI, Michele</creatorcontrib><creatorcontrib>GRAZIA SPILLANTINI, Maria</creatorcontrib><creatorcontrib>CLAUDIO LATAGLIATA, Emanuele</creatorcontrib><creatorcontrib>PASCUCCI, Tiziana</creatorcontrib><creatorcontrib>PUGLISI-ALLEGRA, Stefano</creatorcontrib><creatorcontrib>GARDONI, Fabrizio</creatorcontrib><creatorcontrib>DI LUCA, Monica</creatorcontrib><creatorcontrib>PICCONI, Barbara</creatorcontrib><creatorcontrib>CALABRESI, Paolo</creatorcontrib><creatorcontrib>SILIQUINI, Sabrina</creatorcontrib><creatorcontrib>TOZZI, Alessandro</creatorcontrib><creatorcontrib>TANTUCCI, Michela</creatorcontrib><creatorcontrib>GHIGLIERI, Veronica</creatorcontrib><creatorcontrib>DI FILIPPO, Massimiliano</creatorcontrib><creatorcontrib>PENDOLINO, Valentina</creatorcontrib><creatorcontrib>DE LURE, Antonio</creatorcontrib><creatorcontrib>MARTI, Matteo</creatorcontrib><title>Mechanisms underlying the impairment of hippocampal long-term potentiation and memory in experimental Parkinson's disease</title><title>Brain (London, England : 1878)</title><addtitle>Brain</addtitle><description>Although patients with Parkinson's disease show impairments in cognitive performance even at the early stage of the disease, the synaptic mechanisms underlying cognitive impairment in this pathology are unknown. Hippocampal long-term potentiation represents the major experimental model for the synaptic changes underlying learning and memory and is controlled by endogenous dopamine. We found that hippocampal long-term potentiation is altered in both a neurotoxic and transgenic model of Parkinson's disease and this plastic alteration is associated with an impaired dopaminergic transmission and a decrease of NR2A/NR2B subunit ratio in synaptic N-methyl-d-aspartic acid receptors. Deficits in hippocampal-dependent learning were also found in hemiparkinsonian and mutant animals. Interestingly, the dopamine precursor l-DOPA was able to restore hippocampal synaptic potentiation via D1/D5 receptors and to ameliorate the cognitive deficit in parkinsonian animals suggesting that dopamine-dependent impairment of hippocampal long-term potentiation may contribute to cognitive deficits in patients with Parkinson's disease.</description><subject>alpha-Synuclein - genetics</subject><subject>Analysis of Variance</subject><subject>Animals</subject><subject>Antiparkinson Agents - pharmacology</subject><subject>Antiparkinson Agents - therapeutic use</subject><subject>Benserazide - pharmacology</subject><subject>Benserazide - therapeutic use</subject><subject>Biological and medical sciences</subject><subject>Biophysical Phenomena - drug effects</subject><subject>Biophysical Phenomena - genetics</subject><subject>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</subject><subject>Disease Models, Animal</subject><subject>Dopamine - metabolism</subject><subject>Electric Stimulation</subject><subject>Excitatory Postsynaptic Potentials - drug effects</subject><subject>Excitatory Postsynaptic Potentials - genetics</subject><subject>Excitatory Postsynaptic Potentials - physiology</subject><subject>Exploratory Behavior - drug effects</subject><subject>Hippocampus - physiopathology</subject><subject>Humans</subject><subject>Levodopa - pharmacology</subject><subject>Levodopa - therapeutic use</subject><subject>Long-Term Potentiation - drug effects</subject><subject>Long-Term Potentiation - genetics</subject><subject>Long-Term Potentiation - physiology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Memory Disorders - drug therapy</subject><subject>Memory Disorders - etiology</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Microdialysis - methods</subject><subject>Mutation - genetics</subject><subject>Neurology</subject><subject>Oxidopamine - toxicity</subject><subject>Parkinson Disease - complications</subject><subject>Parkinson Disease - drug therapy</subject><subject>Parkinson Disease - etiology</subject><subject>Parkinson Disease - pathology</subject><subject>Patch-Clamp Techniques</subject><subject>Radionuclide Imaging</subject><subject>Rats</subject><subject>Subcellular Fractions - drug effects</subject><subject>Subcellular Fractions - metabolism</subject><subject>Sympatholytics - toxicity</subject><subject>Synaptosomes - diagnostic imaging</subject><subject>Synaptosomes - drug effects</subject><subject>Tritium - metabolism</subject><subject>Tyrosine 3-Monooxygenase - metabolism</subject><issn>0006-8950</issn><issn>1460-2156</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkE1vFDEMQCNERZfCjTPKBcGBoU4yyeweq4qPSkVwgPPIkzjdwEwyJLOi--_JsguVD7bsZ0t-jL0Q8E7ARl0OGUO8xN9FgHjEVqI10EihzWO2AgDTrDcaztnTUn4AiFZJ84SdS6mNMC2s2P4z2S3GUKbCd9FRHvch3vFlSzxMM4Y8UVx48nwb5jlZrL2RjyneNQvlic9pqfOAS0iRY3R8oinlPQ-R0_1MORzW68ZXzD9DLCm-LtyFQljoGTvzOBZ6fsoX7PuH99-uPzW3Xz7eXF_dNrbV66XpkEh5750VGjR07hBOw9rJViK2nUYaHEEtrRu812RUR4Myg5YK1KAu2Jvj3TmnXzsqSz-FYmkcMVLalb46aUF0HbQVfXtEbU6lZPL9XD_AvO8F9AfZ_V_Z_VF2xV-eLu-Gidx_-J_dCrw6AVgsjj5jtKE8cHojpDRa_QEwXo1R</recordid><startdate>20120601</startdate><enddate>20120601</enddate><creator>COSTA, Cinzia</creator><creator>SGOBIO, Carmelo</creator><creator>MORARI, Michele</creator><creator>GRAZIA SPILLANTINI, Maria</creator><creator>CLAUDIO LATAGLIATA, Emanuele</creator><creator>PASCUCCI, Tiziana</creator><creator>PUGLISI-ALLEGRA, Stefano</creator><creator>GARDONI, Fabrizio</creator><creator>DI LUCA, Monica</creator><creator>PICCONI, Barbara</creator><creator>CALABRESI, Paolo</creator><creator>SILIQUINI, Sabrina</creator><creator>TOZZI, Alessandro</creator><creator>TANTUCCI, Michela</creator><creator>GHIGLIERI, Veronica</creator><creator>DI FILIPPO, Massimiliano</creator><creator>PENDOLINO, Valentina</creator><creator>DE LURE, Antonio</creator><creator>MARTI, Matteo</creator><general>Oxford University Press</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope></search><sort><creationdate>20120601</creationdate><title>Mechanisms underlying the impairment of hippocampal long-term potentiation and memory in experimental Parkinson's disease</title><author>COSTA, Cinzia ; SGOBIO, Carmelo ; MORARI, Michele ; GRAZIA SPILLANTINI, Maria ; CLAUDIO LATAGLIATA, Emanuele ; PASCUCCI, Tiziana ; PUGLISI-ALLEGRA, Stefano ; GARDONI, Fabrizio ; DI LUCA, Monica ; PICCONI, Barbara ; CALABRESI, Paolo ; SILIQUINI, Sabrina ; TOZZI, Alessandro ; TANTUCCI, Michela ; GHIGLIERI, Veronica ; DI FILIPPO, Massimiliano ; PENDOLINO, Valentina ; DE LURE, Antonio ; MARTI, Matteo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c458t-7aee3fffdc150507d7d7dd508d242aa475aebde0aa4cdbff5e637eb36b52303b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>alpha-Synuclein - genetics</topic><topic>Analysis of Variance</topic><topic>Animals</topic><topic>Antiparkinson Agents - pharmacology</topic><topic>Antiparkinson Agents - therapeutic use</topic><topic>Benserazide - pharmacology</topic><topic>Benserazide - therapeutic use</topic><topic>Biological and medical sciences</topic><topic>Biophysical Phenomena - drug effects</topic><topic>Biophysical Phenomena - genetics</topic><topic>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</topic><topic>Disease Models, Animal</topic><topic>Dopamine - metabolism</topic><topic>Electric Stimulation</topic><topic>Excitatory Postsynaptic Potentials - drug effects</topic><topic>Excitatory Postsynaptic Potentials - genetics</topic><topic>Excitatory Postsynaptic Potentials - physiology</topic><topic>Exploratory Behavior - drug effects</topic><topic>Hippocampus - physiopathology</topic><topic>Humans</topic><topic>Levodopa - pharmacology</topic><topic>Levodopa - therapeutic use</topic><topic>Long-Term Potentiation - drug effects</topic><topic>Long-Term Potentiation - genetics</topic><topic>Long-Term Potentiation - physiology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Memory Disorders - drug therapy</topic><topic>Memory Disorders - etiology</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Microdialysis - methods</topic><topic>Mutation - genetics</topic><topic>Neurology</topic><topic>Oxidopamine - toxicity</topic><topic>Parkinson Disease - complications</topic><topic>Parkinson Disease - drug therapy</topic><topic>Parkinson Disease - etiology</topic><topic>Parkinson Disease - pathology</topic><topic>Patch-Clamp Techniques</topic><topic>Radionuclide Imaging</topic><topic>Rats</topic><topic>Subcellular Fractions - drug effects</topic><topic>Subcellular Fractions - metabolism</topic><topic>Sympatholytics - toxicity</topic><topic>Synaptosomes - diagnostic imaging</topic><topic>Synaptosomes - drug effects</topic><topic>Tritium - metabolism</topic><topic>Tyrosine 3-Monooxygenase - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>COSTA, Cinzia</creatorcontrib><creatorcontrib>SGOBIO, Carmelo</creatorcontrib><creatorcontrib>MORARI, Michele</creatorcontrib><creatorcontrib>GRAZIA SPILLANTINI, Maria</creatorcontrib><creatorcontrib>CLAUDIO LATAGLIATA, Emanuele</creatorcontrib><creatorcontrib>PASCUCCI, Tiziana</creatorcontrib><creatorcontrib>PUGLISI-ALLEGRA, Stefano</creatorcontrib><creatorcontrib>GARDONI, Fabrizio</creatorcontrib><creatorcontrib>DI LUCA, Monica</creatorcontrib><creatorcontrib>PICCONI, Barbara</creatorcontrib><creatorcontrib>CALABRESI, Paolo</creatorcontrib><creatorcontrib>SILIQUINI, Sabrina</creatorcontrib><creatorcontrib>TOZZI, Alessandro</creatorcontrib><creatorcontrib>TANTUCCI, Michela</creatorcontrib><creatorcontrib>GHIGLIERI, Veronica</creatorcontrib><creatorcontrib>DI FILIPPO, Massimiliano</creatorcontrib><creatorcontrib>PENDOLINO, Valentina</creatorcontrib><creatorcontrib>DE LURE, Antonio</creatorcontrib><creatorcontrib>MARTI, Matteo</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><jtitle>Brain (London, England : 1878)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>COSTA, Cinzia</au><au>SGOBIO, Carmelo</au><au>MORARI, Michele</au><au>GRAZIA SPILLANTINI, Maria</au><au>CLAUDIO LATAGLIATA, Emanuele</au><au>PASCUCCI, Tiziana</au><au>PUGLISI-ALLEGRA, Stefano</au><au>GARDONI, Fabrizio</au><au>DI LUCA, Monica</au><au>PICCONI, Barbara</au><au>CALABRESI, Paolo</au><au>SILIQUINI, Sabrina</au><au>TOZZI, Alessandro</au><au>TANTUCCI, Michela</au><au>GHIGLIERI, Veronica</au><au>DI FILIPPO, Massimiliano</au><au>PENDOLINO, Valentina</au><au>DE LURE, Antonio</au><au>MARTI, Matteo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mechanisms underlying the impairment of hippocampal long-term potentiation and memory in experimental Parkinson's disease</atitle><jtitle>Brain (London, England : 1878)</jtitle><addtitle>Brain</addtitle><date>2012-06-01</date><risdate>2012</risdate><volume>135</volume><issue>Pt 6</issue><spage>1884</spage><epage>1899</epage><pages>1884-1899</pages><issn>0006-8950</issn><eissn>1460-2156</eissn><abstract>Although patients with Parkinson's disease show impairments in cognitive performance even at the early stage of the disease, the synaptic mechanisms underlying cognitive impairment in this pathology are unknown. Hippocampal long-term potentiation represents the major experimental model for the synaptic changes underlying learning and memory and is controlled by endogenous dopamine. We found that hippocampal long-term potentiation is altered in both a neurotoxic and transgenic model of Parkinson's disease and this plastic alteration is associated with an impaired dopaminergic transmission and a decrease of NR2A/NR2B subunit ratio in synaptic N-methyl-d-aspartic acid receptors. Deficits in hippocampal-dependent learning were also found in hemiparkinsonian and mutant animals. Interestingly, the dopamine precursor l-DOPA was able to restore hippocampal synaptic potentiation via D1/D5 receptors and to ameliorate the cognitive deficit in parkinsonian animals suggesting that dopamine-dependent impairment of hippocampal long-term potentiation may contribute to cognitive deficits in patients with Parkinson's disease.</abstract><cop>Oxford</cop><pub>Oxford University Press</pub><pmid>22561640</pmid><doi>10.1093/brain/aws101</doi><tpages>16</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Brain (London, England : 1878), 2012-06, Vol.135 (Pt 6), p.1884-1899 |
| issn | 0006-8950 1460-2156 |
| language | eng |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | alpha-Synuclein - genetics Analysis of Variance Animals Antiparkinson Agents - pharmacology Antiparkinson Agents - therapeutic use Benserazide - pharmacology Benserazide - therapeutic use Biological and medical sciences Biophysical Phenomena - drug effects Biophysical Phenomena - genetics Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Disease Models, Animal Dopamine - metabolism Electric Stimulation Excitatory Postsynaptic Potentials - drug effects Excitatory Postsynaptic Potentials - genetics Excitatory Postsynaptic Potentials - physiology Exploratory Behavior - drug effects Hippocampus - physiopathology Humans Levodopa - pharmacology Levodopa - therapeutic use Long-Term Potentiation - drug effects Long-Term Potentiation - genetics Long-Term Potentiation - physiology Male Medical sciences Memory Disorders - drug therapy Memory Disorders - etiology Mice Mice, Inbred C57BL Mice, Transgenic Microdialysis - methods Mutation - genetics Neurology Oxidopamine - toxicity Parkinson Disease - complications Parkinson Disease - drug therapy Parkinson Disease - etiology Parkinson Disease - pathology Patch-Clamp Techniques Radionuclide Imaging Rats Subcellular Fractions - drug effects Subcellular Fractions - metabolism Sympatholytics - toxicity Synaptosomes - diagnostic imaging Synaptosomes - drug effects Tritium - metabolism Tyrosine 3-Monooxygenase - metabolism |
| title | Mechanisms underlying the impairment of hippocampal long-term potentiation and memory in experimental Parkinson's disease |
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